Field of the Invention
The present invention relates to a marker for diagnosing diabetic retinopathy, a composition for diagnosing diabetic retinopathy, and a kit for diagnosing diabetic retinopathy. Moreover, the present invention relates to an analysis method for providing information required for the diagnosis of diabetic retinopathy.
Description of the Prior Art
Generally, diabetes is accompanied by various complications and typically causes cardiovascular diseases, diabetic nephropathy, diabetic neuropathy, diabetic retinopathy, etc.
Among them, diabetic retinopathy (DR) is diagnosed in 60% or more of diabetics within 10 years after diagnosis and 90% or more of diabetics within 20 years after diagnosis. Diabetic retinopathy is a microangiopathy caused by diabetes, and the features thereof include alterations in retinal vasculature, vascular occlusion, ischemia, neovascularization, and fibrovascular proliferation. Diabetic retinopathy is the most common cause of loss of vision in adults, and in USA, 12,000-24,000 diabetics lose their vision each year. According to a study, the prevalence of diabetic retinopathy is estimated to be about 40% of diabetics in the USA, and about 8% thereof can lead to loss of vision. Diabetic retinopathy can be classified into early stage, non-proliferative diabetic retinopathy (NPDR) and late-stage, proliferative diabetic retinopathy (PDR) (FIG. 1).
In non-proliferative diabetic retinopathy (NPDR), retinal bleeding, microaneurysm, exudate, retinal edema and the like appear due to the occlusion and change in permeability of retinal capillaries while vision is weakened little by little. In addition, it may be accompanied by diabetic macular edema (DME), and in this stage, vision can be severely reduced.
Proliferative diabetic retinopathy (PDR) is a stage in which ischemia is caused by the occlusion of retinal vessels, and thus neovascularization proliferates. This proliferation progresses from the retina to the vitreous body, and complications, including vitreous hemorrhage caused by vitreoretinal traction, tractional retinal detachment, neovascular glaucoma, etc., occur, and loss of vision progresses.
For diabetic retinopathy, laser treatment or vitreous surgery is generally performed, but there are still many patients in which diabetic retinopathy continues to progress, leading to loss of vision. For this reason, there is an increased need for the early diagnosis and inhibition of progression of diabetic retinopathy and the early treatment of a high-risk group. However, the cause of diabetic retinopathy has not yet been clearly established, and biomarkers for determining the progression of diabetic retinopathy are very limited.
Until now, studies on diabetic retinopathy have been conducted with a focus on biochemical and molecular biological studies on the individual proteins of the vitreous body. In addition, studies on proteins in diabetic retinopathy are also in the stage of profiling (discovery) of vitreous proteins, in which proteins in the vitreous body of patients are identified by 2-DE and mass spectrometry. There are little or studies on the verification and validation of whether these vitreous proteins are expressed in blood or whether these can be used as clinical biomarkers.
Accordingly, there is a need to develop a novel diagnostic marker having high clinical specificity and sensitivity together with an antibody capable of detecting the marker in order to make it possible to early diagnose diabetic retinopathy and easily predict the progression thereof. In addition, there is a need to discover a biomarker for diagnosing non-proliferative diabetic retinopathy (NPDR) in which there is almost no subjective symptom.
Under such circumstances, the present inventors have made extensive efforts to develop a marker useful for the early diagnosis of diabetic retinopathy, and as a result, have discovered a protein specific to diabetic retinopathy and identified a protein, the expression of which increases or decreases in patients having diabetic retinopathy, by a LC-MS/MS method, thereby completing the present invention.